Abstract # 16:

Scheduled for Thursday, June 19, 2008 10:45 AM-10:55 AM: Session 2 (Meeting Room 1GHI) Oral Presentation


REDUCTION OF ACUTE STRESS-INDUCED BEHAVIORS BY A CORTICOTROPIN RELEASING FACTOR RECEPTOR 1 ANTAGONIST IN RHESUS MACAQUES

S. A. Chen1, M. L. Schwandt1, S. G. Lindell1, N. Lopez-Coleman1, L. N. Peele1, R. A. Woodward2, K. L. Robbins3, S. J. Suomi3, M. A. Heilig1 and C. S. Barr1
1NIH/NIAAA, Laboratory of Clinical and Translational Studies, NIH Animal Center, P.O. Box 529 , Poolesville, MD 20837, USA, 2NIH/NICHD, Research Animal Management Branch, 3NIH/NICHD, Laboratory of Comparative Ethology
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     The corticotropin releasing factor (CRF) system is known to play an important role in regulating physiologic and behavioral responses to stress. Genetic and pharmacological studies find that such stress-related behaviors are mediated specifically via the CRF Type 1 Receptor (CRF-1). Despite the fact that CRF-1 distribution and expression differ between rodents and primates, there remains a scarcity of studies examining the effects of a CRF-1 antagonist on stress responding in nonhuman primates. Using a within-subjects crossover drug treatment design across test weeks, young adult male (n=4) and female (n=4) rhesus macaques were injected with a CRF-1 antagonist (10 mg/kg, IV) or vehicle approximately one hour prior to a human intruder stress challenge. A principal components analysis of scored behaviors generated four behavioral factors with Eigenvalues greater than 1.0. These were labeled as ‘agitation’, ‘self-orality’, ‘anxiety’, and ‘exploration’. Controlling for sex and rearing condition, the ‘anxiety’ factor (yawn and teeth grind) increased with the stressor [F(1,16)=7.5, p=0.014], and there was an interaction between drug treatment and stress exposure [F(1,16)=4.9, p<0.05], indicating that treatment with the CRF-1 antagonist blocked the stress-induced increase in these behaviors. These data provide early preclinical evidence of a CRF-1 antagonist's ability to reduce stress-induced behaviors in rhesus macaques and furthermore help validate a model for further study of CRF-1 antagonism on stress-related disorders.